From the outset Grupo Latino Americano De Estudio del Lupus or Latin American Group for the Study of Lupus (GLADEL) had two main objectives:
1. To establish an inception, multiethnic and multinational lupus cohort in order to obtain realistic data from SLE patients in Latin America, and
2. To enhance the understanding of lupus within the Latin American community.
These have arisen from the cohort's original description1 and ensuing papers over the following two decades.
Description of the general characteristics of the GLADEL original cohort
The first GLADEL paper that describes the original cohort1 of over 1200 patients emphasized several issues:
First, Spanish speaking people, considered to be “Hispanic” just for that reason in North America, are indeed an admixture of Mestizo, Caucasian and African Latin American populations.
Second, this paper showed that, compared with Caucasians, mestizo patients experienced:
- Earlier age at onset
- More severe disease
- Higher frequency of renal disease, pericarditis and polyadenopathy
- Regarding renal disease, mestizos develop more and earlier
- Higher maximum disease activity
Lupus in Hispanics (LUMINA) /Mestizos (GLADEL)2
→ Hispanic/Mestizo patients with a large Amerindian ancestral background seem to be at high risk of developing SLE and to experience poorer outcomes than Caucasian patients.
→The USA Hispanic patients from the LUMINA cohort fared less favorably than their Mestizo GLADEL counterparts from Latin America.
→ Genetic analysis identified that US Hispanics had higher Amerindian genetic ancestry than Latin American Mestizos, whereas Mestizos had significantly more European genetic ancestry.
Familial aggregation and characteristics of familial lupus
→ GLADEL patients experienced familial aggregation of SLE, RA, and autoimmune disease in general. A polygenic, additive model was the most appropriate behind the genetic contribution to SLE. Also, the risk for siblings of patients to develop SLE was as high as 293.
→ Familial SLE was not characterized by a more severe form of disease than sporadic lupus. These patients had a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis4.
SLE in males
→ Male patients represented 10% of GLADEL’s cohort. They experienced shorter delay in diagnosis and had a higher frequency of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Also, although not significant, mortality was higher among men5.
→ Male had a higher risk of renal damage.
Pediatric SLE in the GLADEL cohort
→ Pediatric patients from GLADEL experienced a more severe presentation with higher disease activity, major hematological, cutaneous and central nervous system involvement. They accrued SLE ACR criteria earlier and at a greater number than adults6.
GLADEL patients with late-onset SLE
Late-onset SLE in Latin Americans was shown to be7:
→ Milder with lower cumulative SLE criteria, reduced renal/mucocutaneous involvement, and required less use of cyclophosphamide.
→ However, they had a higher risk of death and of ocular, pulmonary, and cardiovascular involvement.
SLE in patients with urban vs rural place of residency
Patients living in Rural areas were more likely to be/have8:
→ Mestizo
→ Lower socioeconomic status, educational level and less likely to have medical insurance coverage
→ Experience more active disease at diagnosis and renal disease occurrence over time
→ But not worse outcomes in terms of disease activity over time, renal damage, overall damage and mortality
Organ involvement in SLE according to the GLADEL cohort.
→ Primary cardiac disease occurred in 14% of GLADEL patients and pericarditis was the most frequent manifestation. ALA ancestry was a risk factor for primary cardiac disease occurrence9
→ Early hematological manifestations are risk factors for their subsequent occurrence. The associations between hemolytic anemia and aPLs and thrombocytopenia were corroborated. Hemolytic anemia contributes independently to damage accrual and diminished survival10
→ Discoid SLE onset reduces the risk of further lupus nephritis in patients with SLE11
→ By contrast, patients with bullous systemic lupus erythematosus are at increased risk of lupus nephritis12
→ Jaccoud’s arthropathy may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or survival13
Antimalarials and SLE in GLADEL
The role of antimalarials in SLE has had a lot of attention in later years and GLADEL findings have provided very useful information in this regard. Antimalarials showed a protective effect on:
→ SLE survival, this was shown to be time dependent (at least six months use of antimalarials needed to achieve this effect)14
→ Occurrence of primary cardiac disease9
→ The reduction of renal disease on the one hand and delay in its occurrence on the other15 16
→ Renal damage
→ Hematological involvement10
→ Serious infections17
→ Higher disease activity early in the disease course18
→ Flares19
Effect of corticosteroids and immunosuppressors
→ Prednisone doses higher than 15 mg/day and use of methylprednisolone pulses were predictive of infections17
→ Early immunosuppressive treatment is predictive of remission20
Low disease activity and remission
→ Older age at diagnosis was protective of flares and predicts achieving low disease activity state20
→ The absence of mucocutaneous, renal and hematologic involvement, the use of immunosuppressive drugs and a lower disease activity early in the course of the disease were predictive of remission20
Damage Accrual in the GLADEL cohort
→ The number of flares patients experience, regardless of their severity, increases the risk of damage accrual21
→ Achieving remission and LDAS reduces from damage accrual22
Classification/diagnostic Criteria’s for SLE applied to the GLADEL cohort
→ SLICC and ACR23
→ Performed at least as well as the ACR criteria
→ Showed a more balanced and clinical representation of each of the organ systems
→ Finally, better performance (earlier diagnosis) was achieved when compared with the physicians’ judgment.
→ EULAR/ACR24
→ In our multiethnic lupus cohort, the 2019 EULAR/ACR new criteria did not achieve the goal of classifying patients earlier than with the two previous criteria sets.
→ Our results reinforce the notion that these new criteria need to be examined in various populations, with different degrees of disease activity, particularly in patients with early disease.
REFERENCES
1 The GLADEL Multinational Latin American Prospective Inception Cohort of 1,214 Patients With Systemic Lupus Erythematosus Ethnic and Disease Heterogeneity Among ‘‘Hispanics’’
Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR, Abadi I, Caeiro F, Alvarellos A, Alarcón-Segovia D; Grupo Latinoamericano de Estudio del Lupus (GLADEL)
Medicine (Baltimore). 2004 Jan;83(1):1-17
DOI: 10.1097/01.md.0000104742.42401.e2
Link: https://pubmed.ncbi.nlm.nih.gov/14747764/
2 Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary
Ugarte-Gil MF, Pons-Estel GJ, Molineros J, Wojdyla D, McGwin G Jr, Nath SK, Pons-Estel BA, Alarcón-Riquelme M, Alarcón GS
Rheumatology (Oxford). 2016 Mar;55(3):436-40
DOI: 10.1093/rheumatology/kev280
Link: https://pubmed.ncbi.nlm.nih.gov/26412809/
3 Familial Aggregation of Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Other Autoimmune Diseases in 1,177 Lupus Patients From the GLADEL Cohort
Alarcón-Segovia D, Alarcón-Riquelme ME, Cardiel MH, Caeiro F, Massardo L, Villa AR, Pons-Estel BA; Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL)
Arthritis Rheum. 2005 Apr;52(4):1138-47
DOI: 10.1002/art.20999
Link: https://pubmed.ncbi.nlm.nih.gov/15818688/
4 Clinical Features, Damage Accrual, and Survival in Patients With Familial Systemic Lupus Erythematosus: Data From a Multi-Ethnic, Multinational Latin American Lupus Cohort
Quintana R, Pons-Estel GJ, Roberts K, Sacnún M, Serrano R, Nieto R, Conti S, Gervasoni V, Catoggio LJ, Soriano ER, Scolnik M, García MA, Alvarellos A, Saurit V, Berbotto GA, Sato EI, Costallat LTL, Neto EFB, Bonfa E, Xavier RM, de Oliveira E Silva Montandon AC, Molina-Restrepo JF, Iglesias-Gamarra A, Guibert-Toledano M, Reyes-Llerena GA, Massardo L, Neira OJ, Cardiel MH, Barile-Fabris LA, Amigo MC, Silveira LH, Torre IG, Acevedo-Vásquez EM, Ugarte-Gil MF, Alfaro-Lozano JL, Segami MI, Chacón-Díaz R, Esteva-Spinetti MH, Gomez-Puerta JA, Alarcón GS, Pons-Estel BA
Lupus. 2020 Jun 30;961203320935184
DOI: 10.1177/0961203320935184
Link: https://pubmed.ncbi.nlm.nih.gov/32605527/
5 Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients
Garcia MA, Marcos JC, Marcos AI, Pons-Estel BA, Wojdyla D, Arturi A, Babini JC, Catoggio LJ, Alarcon-Segovia D
Lupus. 2005;14(12):938-46
DOI: 10.1191/0961203305lu2245oa
Link: https://pubmed.ncbi.nlm.nih.gov/16425573/
6 Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children
Ramírez Gómez LA, Uribe Uribe O, Osio Uribe O, Grisales Romero H, Cardiel MH, Wojdyla D, Pons-Estel BA; Grupo Latinoamericano de Estudio del Lupus (GLADEL), Catoggio LJ, Soriano ER, Imamura PM, Manni JA, Grimaudo S, Sarano J, Maldonado-Cocco JA, Arriola MS, Gómez G, García MA, Marcos AI, Marcos JC, Scherbarth HR, Marino PC, Motta EL, Drenkard C, Gamron S, Buliubasich S, Onetti CM, Caeiro F, Alvarellos A, Saurit V, Gentiletti S, Quagliatto N, Gentiletti AA, Machado D, Abdala M, Palatnik S, Berbotto GA, Battagliotti CA, Sato E, Sella EM, Souza AS, Costallat LT, Bertolo MB, Coimbra IB, Borba Neto EF, Bonfá E, Tavares JC, Brenol, Xavier R, Mucenic T, Cavalcanti Fde S, Duarte AL, Marques CD, Da Silva NA, de O e Silva AC, Pacheco TF, Molina-Restrepo JF, Molina-López J, Iglesias-Gamarra A, Iglesias-Rodríguez A, Egea-Bermejo E, Guzmán-Moreno RA, Restrepo-Suárez JF, Guibert-Toledano M, Reyes-Llerena GA, Massardo L, Gareca N, Jacobelli S, Neira OJ, Guzmán LR, Garcia-Kutzbach A, Castellanos C, Cajas E, Pascual-Ramos V, Barile-Fabris LA, Miranda-Limón JM, Amigo MC, Silveira LH, De La Torre IG, Orozco-Barocio G, Estrada-Contreras ML, del Pozo MJ, Aranda Baca LE, Quezada AU, Huerta-Yáñez GF, Acevedo-Vásquez EM, Alfaro-Lozano JL, Cucho-Venegas JM, Segami MI, Chung CP, Alva-Linares M, Abadi I, Chacón-Díaz R, Al Snih Al Snih S, Esteva-Spinetti MH, Vivas J
Lupus. 2008 Jun;17(6):596-604
DOI: 10.1177/0961203307088006
Link: https://pubmed.ncbi.nlm.nih.gov/18539716/
7 Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?
Catoggio LJ, Soriano ER, Imamura PM, Wojdyla D, Jacobelli S, Massardo L, Chacón Díaz R, Guibert-Toledano M, Alvarellos A, Saurit V, Manni JA, Pascual-Ramos V, Silva de Sauza AW, Bonfa E, Tavares Brenol JC, Ramirez LA, Barile-Fabris LA, De La Torre IG, Alarcón GS, Pons-Estel BA; Grupo Latino Americano De Estudio del Lupus (GLADEL)
Lupus. 2015 Jul;24(8):788-95
DOI: 10.1177/0961203314563134
Link: https://pubmed.ncbi.nlm.nih.gov/25504653/
8 The impact of rural residency on the expression and outcome of systemic lupus erythematosus: data from a multiethnic Latin American cohort
Pons-Estel GJ, Saurit V, Alarcón GS, Hachuel L, Boggio G, Wojdyla D, Alfaro-Lozano JL, de la Torre IG, Massardo L, Esteva-Spinetti MH, Guibert-Toledano M, Gómez LA, Costallat LT, Del Pozo MJ, Silveira LH, Cavalcanti F, Pons-Estel BA
Lupus. 2012 Nov;21(13):1397-404
DOI: 10.1177/0961203312458465
Link: https://pubmed.ncbi.nlm.nih.gov/22941567/
9 Primary cardiac disease in systemic lupus erythematosus patients: protective and risk factors—data from a multi-ethnic Latin American cohort
García MA, Alarcón GS, Boggio G, Hachuel L, Marcos AI, Marcos JC, Gentiletti S, Caeiro F, Sato EI, Borba EF, Brenol JC, Massardo L, Molina-Restrepo JF, Vásquez G, Guibert-Toledano M, Barile-Fabris L, Amigo MC, Huerta-Yáñez GF, Cucho-Venegas JM, Chacón-Diaz R, Pons-Estel BA; Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL)
Rheumatology (Oxford). 2014 Aug;53(8):1431-8
DOI: 10.1093/rheumatology/keu011
Link: https://pubmed.ncbi.nlm.nih.gov/24633413/
10 Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort
González-Naranjo LA, Betancur OM, Alarcón GS, Ugarte-Gil MF, Jaramillo-Arroyave D, Wojdyla D, Pons-Estel GJ, Rondón-Herrera F, Vásquez-Duque GM, Quintana-López G, Da Silva NA, Tavares Brenol JC, Reyes-Llerena G, Pascual-Ramos V, Amigo MC, Massardo L, Alfaro-Lozano J, Segami MI, Esteva-Spinetti MH, Iglesias-Gamarra A, Pons-Estel BA
Semin Arthritis Rheum. 2016 Jun;45(6):675-83
DOI: 10.1016/j.semarthrit.2015.11.003
Link: https://pubmed.ncbi.nlm.nih.gov/26698222/
11 Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort
Pons-Estel GJ, Aspey LD, Bao G, Pons-Estel BA, Wojdyla D, Saurit V, Alvarellos A, Caeiro F, Haye Salinas MJ, Sato EI, Soriano ER, Costallat LT, Neira O, Iglesias-Gamarra A, Reyes-Llerena G, Cardiel MH, Acevedo-Vásquez EM, Chacón-Díaz R, Drenkard C
Lupus. 2017 Jan;26(1):73-83
DOI: 10.1177/0961203316651740
Link: https://pubmed.ncbi.nlm.nih.gov/27230554/
12 LETTER TO THE EDITOR
A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients
Pons-Estel GJ, Quintana R, Alarcón GS, Sacnún M, Ugarte-Gil MF, Pons-Estel BA; on behalf of GLADEL
Lupus 2018. 27(10):1753-1754
DOI: 10.1177/0961203318776104
Link: https://pubmed.ncbi.nlm.nih.gov/29764291/
13 Jaccoud’s arthropathy in SLE: findings from a Latin American multiethnic population
Quintana R, Pons-Estel G, Roberts K, Sacnún M, Berbotto G, Garcia MA, Saurit V, Barile-Fabris L, Acevedo-Vazquez EM, Tavares Brenol JC, Sato EI, Iglesias A, Uribe O, Alarcon G, Pons-Estel BA
Lupus Sci Med. 2019 Aug 12;6(1):e000343
DOI: 10.1136/lupus-2019-000343
Link: https://pubmed.ncbi.nlm.nih.gov/31478011/
14 Antimalarial Treatment May Have a Time-Dependent Effect on Lupus Survival
Shinjo SK, Bonfá E, Wojdyla D, Borba EF, Ramirez LA, Scherbarth HR, Brenol JC, Chacón-Diaz R, Neira OJ, Berbotto GA, De La Torre IG, Acevedo-Vázquez EM, Massardo L, Barile-Fabris LA, Caeiro F, Silveira LH, Sato EI, Buliubasich S, Alarcón GS, Pons-Estel BA; Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL)
Arthritis Rheum. 2010 Mar;62(3):855-62
DOI: 10.1002/art.27300
Link: https://pubmed.ncbi.nlm.nih.gov/20131238/
15 Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort
Pons-Estel GJ, Alarcón GS, Hachuel L, Boggio G, Wojdyla D, Pascual-Ramos V, Soriano ER, Saurit V, Cavalcanti FS, Guzman RA, Guibert-Toledano M, Sauza Del Pozo MJ, Amigo MC, Alva M, Esteva-Spinetti MH, Pons-Estel BA, on behalf of GLADEL
Rheumatology (Oxford). 2012 Jul;51(7):1293-8
DOI: 10.1093/rheumatology/ker514
Link: https://pubmed.ncbi.nlm.nih.gov/22389125/
16 Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: Data from a Latin American cohort
Pons-Estel GJ, Alarcón GS, Burgos PI, Hachuel L, Boggio G, Wojdyla D, Nieto R, Alvarellos A, Catoggio LJ, Guibert-Toledano M, Sarano J, Massardo L, Vásquez GM, Iglesias-Gamarra A, Lavras Costallat LT, Da Silva NA, Alfaro JL, Abadi I, Segami MI, Huerta G, Cardiel MH, Pons-Estel BA; Grupo Latino Americano de Estudio de Lupus (GLADEL)
Lupus. 2013 Aug;22(9):899-907
DOI: 10.1177/0961203313496339
Link: https://pubmed.ncbi.nlm.nih.gov/23857989/
17 Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort
Pimentel-Quiroz VR, Ugarte-Gil MF, Harvey GB, Wojdyla D, Pons-Estel GJ, Quintana R, Esposto A, García MA, Catoggio LJ, Cardiel MH, Barile LA, Amigo MC, Sato EI, Bonfa E, Borba E, Lavras Costallat LT, Neira OJ, Massardo L, Guibert-Toledano M, Chacón-Díaz R, Alarcón GS, Pons-Estel BA
Lupus 2019 Aug;28(9):1101-1110.
DOI: 10.1177/0961203319860579
Link: https://pubmed.ncbi.nlm.nih.gov/31291843/
18 Factors predictive of high disease activity early in the course of SLE in patients from a Latin-American cohort
Pimentel-Quiroz VR, Ugarte-Gil MF, Pons-Estel GJ, Soriano ER, Saurit V, Sato EI, Lavras Costallat LT, Molina JF, Iglesias-Gamarra A, Reyes-Llerena G, Neira OJ, Barile LA, Silveira LH, Segami MI, Chacón-Díaz R, Wojdyla D, Alarcón GS, Pons-Estel BA
Semin Arthritis Rheum. 2017 Oct;47(2):199-203
DOI: 10.1016/j.semarthrit.2017.01.012
Link: https://pubmed.ncbi.nlm.nih.gov/28291583/
19 Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort
Ugarte-Gil MF, Wojdyla D, Pastor-Asurza CA, Gamboa-Cárdenas RV, Acevedo-Vásquez EM, Catoggio LJ, García MA, Bonfá E, Sato EI, Massardo L, Pascual-Ramos V, Barile LA, Reyes-Llerena G, Iglesias-Gamarra A, Molina-Restrepo JF, Chacón-Díaz R, Alarcón GS, Pons-Estel BA
Lupus. 2018 Apr;27(4):536-544
DOI: 10.1177/0961203317728810
Link: https://pubmed.ncbi.nlm.nih.gov/28857715/
20 Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a multi-ethnic, multinational Latin-American Lupus Cohort
Ugarte-Gil MF, Wojdyla D, Pons-Estel GJ, Quintana R, Gómez-Puerta JA, Catoggio LJ, Alvarellos A, Saurit V, Borba E, Sato E, Costallat L, Da Silva NA, Iglesias-Gamarra A, Neira O, Reyes-Llerena G, Cardiel MH, Amigo MC, Acevedo-Vásquez E, Esteva-Spinetti MH, Alarcón GS, Pons-Estel BA.J
J Rheumatol. 2019 Oct;46(10):1299-1308
DOI: 10.3899/jrheum.180433
Link: https://pubmed.ncbi.nlm.nih.gov/30824636/
21 The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort
Ugarte-Gil MF, Acevedo-Vásquez E, Alarcón GS, Pastor-Asurza CA, Alfaro-Lozano JL, Cucho-Venegas JM, Segami MI, Wojdyla D, Soriano ER, Drenkard C, Brenol JC, de Oliveira e Silva Montandon AC, Costallat LT, Massardo L, Molina-Restrepo JF, Guibert-Toledano M, Silveira LH, Amigo MC, Barile-Fabris LA, Chacón-Díaz R, Esteva-Spinetti MH, Pons-Estel GJ, McGwin G Jr, Pons-Estel BA; on behalf of GLADEL
Ann Rheum Dis. 2015 Jun;74(6):1019-23
DOI: 10.1136/annrheumdis-2013-204620
Link: https://pubmed.ncbi.nlm.nih.gov/24525909/
22 Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL)
Ugarte-Gil MF, Wojdyla D, Pons-Estel GJ, Catoggio LJ, Drenkard C, Sarano J, Berbotto GA, Borba EF, Sato EI, Tavares Brenol JC, Uribe O, Ramirez Gómez LA, Guibert-Toledano M, Massardo L, Cardiel MH, Silveira LH, Chacón-Diaz R, Alarcón GS, Pons-Estel BA, On behalf of GLADEL
Annals of the Rheumatic Diseases 76(12):annrheumdis-2017-211814
DOI: 10.1136/annrheumdis-2017-211814
Link: https://pubmed.ncbi.nlm.nih.gov/28939626/
23 The American College of Rheumatology and the Systemic Lupus International Collaborating Clinics Classification criteria for systemic lupus erythematosus in two multiethnic cohorts: a commentary
Pons-Estel GJ, Wojdyla D, McGwin G Jr, Magder LS, Petri MA, Pons-Estel BA; Grupo Latino Americano De Estudio del Lupus (GLADEL), Alarcón GS; on behalf of the LUMINA cohort
Lupus. 2014;23(1):3-9
DOI: 10.1177/0961203313512883
Link: https://pubmed.ncbi.nlm.nih.gov/24285098/
24 Applying the 2019 EULAR/ACR lupus criteria to patients from an established cohort: a Latin American perspective
Pons-Estel GJ, Ugarte-Gil MF, Harvey GB, Wojdyla D, Quintana R, Saurit V, Soriano ER, Bonfa E, Massardo L, Cardiel M, Vila LM, Griffin R, Pons-Estel BA, Alarcón GS; Grupo Latino Americano De Estudio de Lupus (GLADEL)
RMD Open. 2020 Jan;6(1):e001097
DOI: 10.1136/rmdopen-2019-001097
Link: https://pubmed.ncbi.nlm.nih.gov/31958284/
